scholarly journals CPT1A Over-Expression Increases Reactive Oxygen Species in the Mitochondria and Promotes Antioxidant Defenses in Prostate Cancer

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3431 ◽  
Author(s):  
Molishree Joshi ◽  
Jihye Kim ◽  
Angelo D’Alessandro ◽  
Emily Monk ◽  
Kimberley Bruce ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Reactive Oxygen Species ◽  
Environmental Changes ◽  
Reactive Oxygen ◽  
Progression Free Survival ◽  
Antioxidant Defenses ◽  
Oxygen Species ◽  
Altered Expression ◽  
Lipid Catabolism ◽  
Mitochondrial Ros

Cancers reprogram their metabolism to adapt to environmental changes. In this study, we examined the consequences of altered expression of the mitochondrial enzyme carnitine palmitoyl transferase I (CPT1A) in prostate cancer (PCa) cell models. Using transcriptomic and metabolomic analyses, we compared LNCaP-C4-2 cell lines with depleted (knockdown (KD)) or increased (overexpression (OE)) CPT1A expression. Mitochondrial reactive oxygen species (ROS) were also measured. Transcriptomic analysis identified ER stress, serine biosynthesis and lipid catabolism as significantly upregulated pathways in the OE versus KD cells. On the other hand, androgen response was significantly downregulated in OE cells. These changes associated with increased acyl-carnitines, serine synthesis and glutathione precursors in OE cells. Unexpectedly, OE cells showed increased mitochondrial ROS but when challenged with fatty acids and no androgens, the Superoxide dismutase 2 (SOD2) enzyme increased in the OE cells, suggesting better antioxidant defenses with excess CPT1A expression. Public databases also showed decreased androgen response correlation with increased serine-related metabolism in advanced PCa. Lastly, worse progression free survival was observed with increased lipid catabolism and decreased androgen response. Excess CPT1A is associated with a ROS-mediated stress phenotype that can support PCa disease progression. This study provides a rationale for targeting lipid catabolic pathways for therapy in hormonal cancers.

Reserpine Induces Apoptosis and Cell Cycle Arrest in Hormone Independent Prostate Cancer Cells through Mitochondrial Membrane Potential Failure

2019 ◽  
Vol 18 (9) ◽  
pp. 1313-1322 ◽  
Author(s):  
Manjula Devi Ramamoorthy ◽  
Ashok Kumar ◽  
Mahesh Ayyavu ◽  
Kannan Narayanan Dhiraviam
Keyword(s):  
Prostate Cancer ◽  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Membrane Potential ◽  
Cancer Cells ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Prostate Cancer Cells

Background: Reserpine, an indole alkaloid commonly used for hypertension, is found in the roots of Rauwolfia serpentina. Although the root extract has been used for the treatment of cancer, the molecular mechanism of its anti-cancer activity on hormonal independent prostate cancer remains elusive. Methods: we evaluated the cytotoxicity of reserpine and other indole alkaloids, yohimbine and ajmaline on Prostate Cancer cells (PC3) using MTT assay. We investigated the mechanism of apoptosis using a combination of techniques including acridine orange/ethidium bromide staining, high content imaging of Annexin V-FITC staining, flow cytometric quantification of the mitochondrial membrane potential and Reactive Oxygen Species (ROS) and cell cycle analysis. Results: Our results indicate that reserpine inhibits DNA synthesis by arresting the cells at the G2 phase and showed all standard sequential features of apoptosis including, destabilization of mitochondrial membrane potential, reduced production of reactive oxygen species and DNA ladder formation. Our in silico analysis further confirmed that indeed reserpine docks to the catalytic cleft of anti-apoptotic proteins substantiating our results. Conclusion: Collectively, our findings suggest that reserpine can be a novel therapeutic agent for the treatment of androgen-independent prostate cancer.

A 60-Hz sinusoidal magnetic field induces apoptosis of prostate cancer cells through reactive oxygen species

2008 ◽  
Vol 84 (11) ◽  
pp. 945-955 ◽  
Author(s):  
Eui Kwan Koh ◽  
Byung-Kyu Ryu ◽  
Dong-Young Jeong ◽  
Iel-Soo Bang ◽  
Myung Hee Nam ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Prostate Cancer ◽  
Reactive Oxygen Species ◽  
Cancer Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Prostate Cancer Cells ◽  
Sinusoidal Magnetic Field

Exploring the Potentials of Antioxidants in Retarding Ageing

2017 ◽  
pp. 166-195 ◽  
Author(s):  
Minu Kesheri ◽  
Swarna Kanchan ◽  
Rajeshwar P. Sinha
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Growth And Development ◽  
Aging Process ◽  
Reactive Oxygen ◽  
Normal Growth ◽  
Antioxidant Defenses ◽  
Oxygen Species ◽  
Biotic Stresses ◽  
Living Organisms

In retrospect to the rise in the occurrence of ageing related disorders and the everlasting desire to overcome ageing, exploring the causes, mechanisms and therapies to curb ageing becomes relevant. Reactive Oxygen Species (ROS) are commonly generated during normal growth and development. However abiotic and biotic stresses enhance the level of ROS which in turn pose the threat of oxidative stress. Ability to perceive ROS and to speedily commence antioxidant defenses is crucial for the survival as well as longevity of living cells. Therefore living organisms are bestowed with antioxidants to combat the damages caused by oxidative stress. This chapter aims to elucidate an overview of the process of ageing, generation and enhancement of reactive oxygen species, damages incurred by oxidative stress, its amelioration strategies, therapeutic and biotechnological potentials of antioxidants and various sources of bioactive compounds significant in retardation of aging process.

scholarly journals Protein Kinase D Mediates Mitochondrion-to-Nucleus Signaling and Detoxification from Mitochondrial Reactive Oxygen Species

2005 ◽  
Vol 25 (19) ◽  
pp. 8520-8530 ◽  
Author(s):  
Peter Storz ◽  
Heike Döppler ◽  
Alex Toker
Keyword(s):  
Reactive Oxygen Species ◽  
Transcription Factor ◽  
Protein Kinase ◽  
Reactive Oxygen ◽  
Protein Kinase D ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Mitochondrial Oxidative Stress ◽  
Cellular Survival ◽  
Mitochondrial Ros

ABSTRACT Efficient elimination of mitochondrial reactive oxygen species (mROS) correlates with increased cellular survival and organism life span. Detoxification of mitochondrial ROS is regulated by induction of the nuclear SOD2 gene, which encodes the manganese-dependent superoxide dismutase (MnSOD). However, the mechanisms by which mitochondrial oxidative stress activates cellular signaling pathways leading to induction of nuclear genes are not known. Here we demonstrate that release of mROS activates a signal relay pathway in which the serine/threonine protein kinase D (PKD) activates the NF-κB transcription factor, leading to induction of SOD2. Conversely, the FOXO3a transcription factor is dispensable for mROS-induced SOD2 induction. PKD-mediated MnSOD expression promotes increased survival of cells upon release of mROS, suggesting that mitochondrion-to-nucleus signaling is necessary for efficient detoxification mechanisms and cellular viability.

Sign in / Sign up

Export Citation Format

Share Document